Toxicology

Buprenorphine Induction: Where We Are and Where We’re Headed

Buprenorphine, a partial µ opioid receptor agonist, has been approved by the Food and Drug Administration for outpatient opioid dependence pharmacotherapy since 2002.1

Multiple settings have proven to be safe for buprenorphine, with evolving literature on efficacy in these variable practices. Two well-researched settings for induction include the unobserved induction and induction in the emergency department.

Since the early 2000s, a safe alternative to physician-observed induction of buprenorphine has been off-site, “home,”or unobserved induction. In a home induction, a patient is evaluated prior to beginning treatment. Eligible patients are often still using opioids and not experiencing active withdrawal. If eligible, the patient receives a buprenorphine prescription and self-administers the first dose of buprenorphine unobserved. Recent descriptions of home induction approaches prescribed in two Boston practices (as well as many other studies on unobserved induction) revealed the practice to be safe and found no differences between groups in longitudinal outcomes.2,3

A 2007 Massachusetts survey indicated that 42% of physicians had adopted home induction as regular practice.4 A 2008 study of more than 100 patients undergoing home induction found that a home buprenorphine induction protocol resulted in no observed serious adverse events, few reported induction complications, and treatment retention rates consistent with previous studies.5

Suboxone induction is also undergone frequently with less forward-planning than unobserved induction. Many of these inductions happen in the emergency department. Since the publication of a landmark trial demonstrating the efficacy of buprenorphine induction for ED patients with opioid use disorders (OUDs), emergency departments across the United States have developed protocols for facilitating buprenorphine induction.6 Studies have reported that induction of buprenorphine in the ED, when compared to control, resulted in higher engagement in addiction treatment. Despite this, significant gaps in access to treatment remain. One analysis suggested that only one in three patients who screen positive for OUD actually receive treatment for OUD.7

A third setting, undergoing active research, is emerging as a potential solution to a subset of patients who would not otherwise access buprenorphine. Immediate initiation of buprenorphine after opioid overdose reversal with naloxone in the field by trained emergency medical technicians (EMT) was first reported in New Jersey. In the first U.S. study of its kind, investigators did not report any complications with subsequent induction of buprenorphine once the patients reached the ED. This novel induction strategy suggests that immediate administration of buprenorphine after naloxone is safe and valuable for emergency medical service clinicians.8

The decision on which patients are appropriate for buprenorphine induction is well-researched. A 2020 review of 14 peer-reviewed manuscripts and 11 scientific abstracts related to OUD treatment in the emergency department reported variable inclusion and exclusion criteria.

This review found that inclusion criteria have most often been a diagnosis of OUD age over 18, a positive urine test for opioids, recent or multiple visits related to overdose, intoxication, or admission to an ED observation unit.

Exclusion criteria were pregnancy, current enrollment in an OUD treatment program, abuse of benzodiazepines or alcohol, liver disease, critically ill patients, active suicidality, police custody, or an inability to communicate due to dementia or psychosis.

While ED studies have often excluded pregnant patients, research outside of emergency settings has shown that buprenorphine is safe and effective for pregnant patients.9

In deciding dosing for initial induction, most studies report an initial dose ranging from 2 mg to 8 mg with consistent maximum doses reported around 16 mg and as high as 32 mg.9

There is also extensive research offering general guidance for dosing and timing of induction. Most protocols use the Clinical Opioid Withdrawal Scale (COWS) to assess withdrawal severity. The COWS is a clinician-administered tool for assessing a patient’s level of opioid withdrawal by rating 11 commonly seen opioid withdrawal symptoms.12

Clinical assessment of withdrawal is imperative for decreasing the risk of precipitated withdrawal. Precipitated withdrawal is a particularly worrisome adverse effect. This occurs when a patient undergoes induction too soon after use of another opioid agonist. The patient experiences an immediate withdrawal syndrome due to displacement of that agonist by buprenorphine, a partial agonist with high affinity.

Precipitated withdrawal can largely be avoided by only commencing induction in a patient with objective evidence of opioid withdrawal. There are no strict cutoff criteria based on COWS score, but studies in the aforementioned 2020 review used COWS score cutoffs as low as 6 and as high as 13.9

In conclusion, buprenorphine has been shown to be a safe and effective medication in multiple settings with extensive research on both unobserved induction and physician-observed induction. Emerging evidence suggests that EMT-observed induction of buprenorphine may represent a third setting that could allow another subset of patients to access treatment. In planning how this might come to fruition, numerous studies exist to help guide decisions on patients to include/exclude, timing of induction, and dosing.


References

  1. Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2004.
  2. Mintzer IL, Eisenberg M, Terra M, MacVane C, Himmelstein DU, Woolhandler S. Treating opioid addiction with buprenorphine-naloxone in community-based primary care settings. Ann Fam Med. 2007;5(2):146–50.
  3. Alford DP, LaBelle CT, Richardson JM, et al. Treating homeless opioid dependent patients with buprenorphine in an office-based setting. J Gen Intern Med. 2007;22(2):171–6.
  4. Walley AY, Alperen JK, Cheng DM, et al. Office-based management of opioid dependence with buprenorphine: clinical practices and barriers. J Gen Intern Med. 2008;23(9):1393–8.
  5. Lee JD, Grossman E, DiRocco D, Gourevitch MN. Home buprenorphine/naloxone induction in primary care. J Gen Intern Med. 2009;24(2):226-232.
  6. D’Onofrio G, O’Connor PG, Pantalon MV, et al. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA. 2015;313(16):1636–1644.
  7. D’Onofrio G, Edelman EJ, Hawk KF, et al. Implementation facilitation to promote emergency department-initiated buprenorphine for opioid use disorder: protocol for a hybrid type III effectiveness-implementation study (Project ED HEALTH). Implement Sci. 2019;14(1):48.
  8. Carroll GG, Wasserman DD, Shah AA, et al. Buprenorphine Field Initiation of ReScue Treatment by Emergency Medical Services (Bupe FIRST EMS): A Case Series. Prehosp Emerg Care. 2020;1–6.
  9. Cao SS, Dunham SI, Simpson SA. Prescribing Buprenorphine for Opioid Use Disorders in the ED: A Review of Best Practices, Barriers, and Future Directions. Open Access Emerg Med. 2020;12:261-274.
  10. Kaucher KA, Caruso EH, Sungar G, et al. Evaluation of an emergency department buprenorphine induction and medication-assisted treatment referral program. Am J Emerg Med. 2020;38(2):300–304.
  11. Herring AA, Perrone J, Nelson LS. Managing Opioid Withdrawal in the Emergency Department With Buprenorphine. Ann Emerg Med. 2019;73(5):481–487.
  12. Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003;35(2):253–259.

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